The overriding aim of this proposal is to increase our understanding of the genetic mechanisms regulating male social behaviors. Most of our knowledge concerning social behavior has been based on classic work in which the relationship between the steroid hormones and behaviors were delineated: in most laboratory rodent species and mammals in the wild, male social behavior occurs during the breeding season and is highly dependent upon the concurrent availability of gonadal steroids. However, between individuals and across species, the dependence of steroids in male social behavior is highly variable, and our lack of knowledge concerning the genetic underpinnings of these behaviors remains a major obstacle to understanding human male behaviors normally thought to be dependent on gonadal steroids. To investigate this, the model species used will be hybrid B6D2F1 male mice in which a large proportion retains the complete repertoire of male social and copulatory behaviors long after orchidectomy. We have completed a bioinformatic analysis of gene expression arrays comparing mRNA from critical sites known to mediate male social behavior, the medial preoptic area and the bed nucleus of the stria terminalis, between hybrid mice that persist and those that cease to interact socially after orchidectomy. Our analysis has linked six novel candidate genes to complex social behaviors. The specific aims of this proposal are to validate the results of microarray analysis and then test the role of the candidate genes in gonadal steroid-independent male social behavior. Project Narrative: Social relationships are important for quality of life for people at all ages, but especially in senior citizens and patient populations. Specific groups that would benefit from this research include aging men experiencing declining testosterone concentrations and prostate cancer survivors that, despite new radiation and surgical treatments and the introduction of sildenafil, the vast majority report dissatisfaction with the quality of their intimate relationships. It is our hope that this research may ultimately be utilized in the near future to develop new treatments for erectile dysfunction in men.